This renewal seeks support to continue to promote and facilitate the effective and timely usage of the advanced, evolving techniques of computerized mass spectrometry in solving biochemical, biological and biomedical research problems involving current questions of recognized scientific significance at the molecular level. Mass spectrometry will provide new experimental structural insight in addressing structure-function issues involving the proteins, carbohydrates and nucleic acids in molecular cell biology. This program will continue its pro-active role in bringing to the basic and clinical scientists the experimental benefits of these methods based upon state-of-the-art instrumentation, by providing the expertise required to formulate and execute appropriate experimental strategies to solve their biomedical problems. This is of essential importance since scientists and clinicians at the forefront of their disciplines have neither the interest nor the capability in developing advanced mass spectrometric based methods for use in their own important problem areas. In addition, the magnitude of necessary capital and operating costs requires that this technology be made available on a shared national resource basis. We will continue to provide broad facility faculty and staff expertise to the biological and biomedical sciences nationally on both a collaborative and service basis. We will maintain our preeminence through active research involvement in key areas of structural biology and medicine, including: 1 ) proteins and glycoconjugates and 2) membrane bound proteins such as enzymes and receptors in symbiosis with key emphasis on the development of micro sample handling, derivatization and separation methodologies as well as pursuit of ultimate sensitivities in tandem mass spectrometry. The program's emphasis is on interdisciplinary research projects that require molecular identification and are directly related to major national concerns in human health. These concerns involve the molecular biology of diseases which are infectious, genetic and of unknown causes. The Facility faculty are addressing these health problems in fundamental areas of biochemistry and cell biology such as posttranslational and xenobiotic modifications of proteins, sequencing of new proteins isolated from 2-d gels, the nature of protein and lipid glycosylation, protein function regulation via phosphorylation, glycosylation, etc., protein tyrosine kinases, receptors, glycolipids, DNA binding proteins, antigen epitopes, antibody recognition, etc.